Biomedical subjects

A Kovac

Publications and source records attributed to A Kovac.

At least 19 recordsLinked to original sources

PubMed2005

A randomized, double-blind, close-ranging, pilot study of intravenous granisetron in the prevention of postoperative nausea and vomiting in patients abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: Postoperative nausea and vomiting (PONV) is a frequent and unpleasant experience that may increase postoperative complications and costs. For surgical procedures with a high risk of PONV, prevention is preferable to treatment. In this study, the authors explore the dose-response relationship between granisetron administered just prior to the end of surgery and post-operative nausea and vomiting in patients undergoing abdominal hysterectomy. METHODS: This was a randomized, double-blind, placebo-controlled, pilot study of post-operative nausea and vomiting prevention. Patients undergoing elective open abdominal hysterectomy requiring general anaesthesia received a single dose of granisetron 0.1, 0.2 or 0.3 mg or placebo administered approximately 15 min prior to the end of surgery. The primary efficacy end-point was the proportion of patients with no vomiting in the 0--6 h interval following medication administration. No inferential statistics were planned. RESULTS: The proportion of patients with no vomiting episode in the 0--6 h interval after administration of study medication was higher in each granisetron treatment group (>90%) than in the placebo group (77%). Proportions of patients with no vomiting episodes in the 0--24 h interval were similar across treatment groups. Results of analyses of proportions of patients with no moderate or severe nausea episodes, proportions of those requiring rescue medication and times to first use of rescue medication suggested a treatment effect of granisetron relative to placebo in both the 0--6 and 0--24 h intervals. Similar proportions of patients in each treatment group reported at least one adverse event. CONCLUSIONS: Granisetron at doses of 0.1, 0.2 and 0.3 mg administered just prior to the end of surgery suggested a trend of improved efficacy compared to placebo in preventing postoperative nausea and vomiting in the first 6 h after abdominal hysterectomy. This pilot study did not identify a dose-response relationship.

Adult↗

PubMed2001

Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages.

Virchow-Robin's perivascular spaces lie between the basement membrane around pericytes and the basement membrane at the surface of the glia limitans of the brain vessels. They are directly connected to the subpial space and harbour a population of cells distinct from pericytes, perivascular microglia and other cells within perivascular spaces (e.g. T cells and mast cells) in their ability to quickly phagocytose particles from the cerebrospinal fluid (CSF). Morphology, function, and cell surface proteins of these perivascular cells suggest an origin from the monocyte/macrophage lineage. It is currently unclear to what extent these brain perivascular cells represent a resident population of histiocytes or undergo continuous supplementation from blood monocytes. Using transplants of green-fluorescent-protein (GFP)-transfected bone marrow cells, we therefore investigated the replacement of perivascular cells by blood-borne macrophages in adult mice. GFP-positive cells in the perivascular spaces were found as early as 2 weeks post transplantation. The substitution of host perivascular cells by donor-derived macrophages was then evaluated using immunocytochemistry and intraventricular injection of hydrophilic rhodamine-fluorescent tracers. Such tracers diffuse along perivascular spaces and are subsequently phagocytosed by perivascular cells leading to stable phagocytosis-dependent labelling. Thus, the population of newly immigrated macrophages could be related to the total number of perivascular macrophages. This approach revealed a continuous increase of donor-derived perivascular cells. At 14 weeks post transplantation, all perivascular cells were donor-derived. These data show that brain perivascular cells are a population of migratory macrophages and not resident histiocytes.

Animals↗

PubMed2000

[Treatment of ascites with reinfusion of ascitic fluid concentrate].

Ascites which is refractory to common therapeutical measures is a great problem. It deteriorates patient's life and is a sign of poor prognosis. Different methods of peritoneal fluid reinfusion belong to effective non-pharmaceutical therapeutic approaches. Main target of this study was to analyse the effectiveness and safety of peritoneal fluid reinfusion and to compare two methods of its administration (i.v. reinfusion and intraperitoneal reinfusion). During three years we have performed 97 reinfusions in 4 patients (2 women and 2 men; mean age 56 years). I.v. reinfusion was administered 68 times and intraperitoneal ewinfusion was performed 28 times. Usually we evacuated 8000 ml of ultrafiltrate. The most common complications were haemoperitoneum (6x) and short-term chills (2x). We didn't have any complications such as coagulopathy, peritonitis or circulation collapse. Intraperitoneal administration seems to be more advantageous when compared with i.v. application, because of less frequent detection of fibrin degradation products and D-dimers after the procedure and higher diuresis during the following days. (Tab. 2, Fig. 5, Ref. 13.).

Ascites↗

PubMed1999

Reduced resource utilization in patients treated for postoperative nausea and vomiting with dolasetron mesylate. MCPR44 Study Group.

STUDY OBJECTIVE: To compare the effect of four different increasing increasing intravenous (i.v.) doses of dolasetron mesylate (12.5 mg, 25 mg, 50 mg, and 100 mg) versus placebo on resource utilization in patients who experienced and were treated for postoperative nausea and vomiting (PONV). DESIGN: Prospective, double-blind, randomized, multicenter study. PATIENTS: 620 ASA physical status I, II, and III male and female outpatients scheduled for surgery with general anesthesia. INTERVENTIONS: Patients who experienced postoperative nausea (duration > or = 5 min, self-reported as moderate to severe) or vomiting (> or = 1 emetic episode) within 2 hours of arrival in the postanesthesia care unit (PACU) were given a single i.v. dose of dolasetron mesylate (12.5 mg, 25 mg, 50 mg, or 100 mg) or placebo infused for at least 30 seconds. MEASUREMENTS AND MAIN RESULTS: Resource utilization in the PACU was assessed by time spent by nurses and/or doctors with patients for PONV and the use of hospital resources such as patient/bed linens and staff/emesis supplies. A significantly (p < 0.05) lower proportion of dolasetron-treated patients compared to placebo-treated patients required new patient/bed linens and staff/emesis supplies. Patients in the placebo group required the greatest amount of care from nurses and/or doctors compared to patients receiving dolasetron. CONCLUSIONS: Treatment with dolasetron can significantly decrease the utilization of emesis supplies and other hospital resources, including staff/emesis supplies and patient/bed linens. In addition, patients receiving dolasetron used fewer health care resources in time spent by hospital personnel than patients who were not treated with dolasetron.

Adult↗

PubMed1999

Stereoselectivity of Mucorales lipases toward triradylglycerols--a simple solution to a complex problem.

The lipases from Rhizopus and Rhizomucor are members of the family of Mucorales lipases. Although they display high sequence homology, their stereoselectivity toward triradylglycerols (sn-2 substituted triacylglycerols) varies. Four different triradylglycerols were investigated, which were classified into two groups: flexible substrates with rotatable O'-C1' ether or ester bonds adjacent to C2 of glycerol and rigid substrates with a rigid N'-C1' amide bond or a phenyl ring in sn-2. Although Rhizopus lipase shows opposite stereopreference for flexible and rigid substrates (hydrolysis in sn-1 and sn-3, respectively), Rhizomucor lipase hydrolyzes both groups of triradylglycerols preferably in sn-1. To explain these experimental observations, computer-aided molecular modeling was applied to study the molecular basis of stereoselectivity. A generalized model for both lipases of the Mucorales family highlights the residues mediating stereoselectivity: (1) L258, the C-terminal neighbor of the catalytic histidine, and (2) G266, which is located in a loop contacting the glycerol backbone of a bound substrate. Interactions with triradylglycerol substrates are dominated by van der Waals contacts. Stereoselectivity can be predicted by analyzing the value of a single substrate torsion angle that discriminates between sn-1 and sn-3 stereopreference for all substrates and lipases investigated here. This simple model can be easily applied in enzyme and substrate engineering to predict Mucorales lipase variants and synthetic substrates with desired stereoselectivity.

Amino Acid Sequence↗

PubMed1999

[Treatment of renal anemia with erythropoietin].

During the last decade, a considerable amount of new information has accumulated regarding therapy optimalization of renal anaemia with recombinant human erythropoietin (EPO). Key question involved is EPO hyporesponsiveness caused by absolute or functional iron deficiency. Most controversial issue in the treatment of renal anaemia in patients with chronic renal insufficiency is the definition of optimal target haemoglobin. Many questions about optimizing EPO therapy were considered at the 2nd European Epoetin Symposium which was held in April 1998 on Crete. Discussion was devoted also to revision of a draft version of the European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure. The presented review is on summary of new insights presented at the symposium. (Ref. 85.)

Anemia↗

PubMed1998

Treatment of end-stage renal disease in central and eastern Europe: overview of current status and future needs.

The situation of end-stage renal disease (ESRD) patients in central and eastern Europe was very poor for many years during the so called socialistic era. Economical and political liberation resulted in the significant growth of renal replacement facilities in this region. The number of hemodialysis units increased significantly (56%) during the period 1990-1996, and the number of patients treated with this modality has risen by 75%. More dramatic progress was achieved in peritoneal dialysis. The number of units performing this method of renal replacement therapy (RRT) increased by 277% and the number of patients by more than 300%. Not only quantitative but also qualitative changes were observed. More modern hemodialysis machines installed in the vast majority of units allow for the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium profile modeling. Also, a wider choice of biocompatible dialyzers has become available during the last few years. The number of centers performing renal transplantation has increased significantly, but the number of renal transplants has not followed this progress. Despite all the progress, further development of all RRT methods is necessary to achieve acceptance rates comparable to those observed in developed countries.

Europe↗

PubMed1998

Evolution of renal replacement therapy in Central and Eastern Europe 7 years after political and economical liberation. Central and Eastern Europe Advisory Board in Chronic Renal Failure.

PURPOSE OF THE STUDY: The conditions of renal replacement therapy (RRT) were very poor in the countries located in Central and Eastern Europe (CEE) when they were members of the so-called 'socialist bloc'. The aim of the present analysis was to document the impact of the socioeconomic changes on dialysis therapy in the CEE countries. DESIGN: This was a special survey with the participation of 12 CEE countries, with data obtained through national registries (with the exception of Russia). RESULTS: During the period 1990-1996 the number of haemodialysis units increased by 56% and the number of centres performing peritoneal dialysis by 296%. The number of patients increased respectively by 78% (haemodialysis) and 306% (peritoneal dialysis). The percentage of patients with diabetic nephropathy and elderly patients rose dramatically during this period. One of the main reasons of such expansion was the rapid development of peritoneal dialysis programmes in the majority of the CEE countries. The introduction of modern haemodialysis machines and a wider choice of different dialysers and concentrates permitted individualization of dialysis procedures. These points and the wider use of erythropoietin had a positive influence on quality of life and treatment outcome. There was also a notable increase in the number of transplant centres, but less so of the number of transplanted patients. CONCLUSION: Renal replacement therapy experienced a major expansion in the CEE countries. Despite the progress achieved, the level of RRT is not yet completely satisfactory in most CEE countries.

Europe↗

PubMed1998

Rational design of Rhizopus oryzae lipase with modified stereoselectivity toward triradylglycerols.

The binding site of sn-1(3)-regioselective Rhizopus oryzae lipase (ROL) has been engineered to change the stereoselectivity of hydrolysis of triacylglycerol substrates and analogs. Two types of prochiral triradylglycerols were considered: 'flexible' substrates with ether, benzylether or ester groups, and 'rigid' substrates with amide or phenyl groups, respectively, in the sn-2 position. The molecular basis of sn-1(3) stereoselectivity of ROL was investigated by modeling the interactions between substrates and ROL, and the model was confirmed by experimental determination of the stereoselectivity of wild-type and mutated ROL. For the substrates, the following rules were derived: (i) stereopreference of ROL toward triradylglycerols depends on the substrate structure. Substrates with 'flexible' sn-2 substituents are preferably hydrolyzed at sn-1, 'rigid' substrates at sn-3. (ii) Stereopreference of ROL toward triradylglycerols can be predicted by analyzing the geometry of the substrate docked to ROL: if the torsion angle phiO3-C3 of glycerol is more than 150 degrees, the substrate will preferably be hydrolyzed in sn-1, otherwise in sn-3. For ROL, the following rules were derived: (i) residue 258 affects stereoselectivity by steric interactions with the sn-2 substituent rather than polar interactions. To a lower extent, stereoselectivity is influenced by mutations further apart (L254) from residue 258. (ii) With 'rigid' substrates, increasing the size of the binding site (mutations L258A and L258S) shifts stereoselectivity of hydrolysis toward sn-1, decreasing its size (L258F and L258F/L254F) toward sn-3.

Glycerol↗

PubMed1996

Hydrolysis and esterification of acylglycerols and analogs in aqueous medium catalyzed by microbial lipases.

The stereoselectivity of microbial lipases from Chromobacterium viscosum (CVL) and Rhizopus arrhizus (RAL) towards monoacylglycerols (rac-1(3)-oleoylglycerol and 2-oleoylglycerol), diacylglycerols (1,3-dioleoylglycerol and rac-1,2(2,3)-dioleoylglycerol) and 2-O-ether analogs (rac-1(3)-oleoyl-2-O-hexadecylglycerol and rac-1(3)-octanoyl-2-O-hexadecylglycerol) was determined. The results of the hydrolysis of 2-O-ether analogs confirmed the importance of the substituent at C-2 of acylglycerols in the stereoselective recognition by microbial lipases and also showed that acylation of mono- and diradylglycerols with oleic acid overlaps the hydrolysis reaction in aqueous medium. With the short-chain, water-soluble octanoic acid no significant esterification occurred. Using rac-1,2(2,3)-dioleoylglycerol as a substrate for the hydrolysis with RAL and CVL, the appearance of 1,3-dioleoylglycerol and of 1(3)-monooleoylglycerol was demonstrated. The possibility of chemical vs. enzyme-catalyzed isomerization of 1,2-dioleoylglycerol and of 2-oleoylglycerol is discussed.

Chromobacterium↗

PubMed1995

Stereoselectivity of microbial lipases. The substitution at position sn-2 of triacylglycerol analogs influences the stereoselectivity of different microbial lipases.

In the present study, the stereoselectivity of purified lipases from Candida rugosa, Chromobacterium viscosum, Pseudomonas species and Rhizopus arrhizus towards triacylglycerols in comparison to various structural analogs were investigated. Different triacylglycerol analogs with distinct polarities at position sn-2 of the glycerol backbone (1,3-diacyl-2-X-glycerol, where 2-X = 2-acyloxy, 2-alkyloxy, 2-deoxy-2-alkyl, or 2-deoxy-2-phenyl) were synthesized. Substrate hydrophobicity and steric requirement was modified by variation of the alkyl and acyl chain length. Hydrolysis of these substrates demonstrated that minor structural variations at C2 of triacylglycerol strongly affect the stereoselectivity of the lipases tested. It was noteworthy that the variation of substrate structure did not only affect the quantity of stereoselectivity expressed as percentage enantiomeric excess, but also resulted in a reversal of stereopreference in some cases. Replacement of the acylester in position 2 of glycerol by a non-ester-linked aliphatic moiety shifted the preference of Chromobacterium viscosum lipase from sn-3 to sn-1. Lipases from Chromobacterium viscosum. Pseudomonas species and Rhizopus arrhizus exhibited sn-3 preference with 2-deoxy-2-phenyl analogs, while towards substrates with a 2-deoxy-2-alkyl moiety sn-1 stereobias was recorded. Candida rugosa lipase was rather insensitive to substrate variations concerning the polarity at position 2 of the glycerol backbone. However, variation of the acyl chain length significantly influenced stereoselectivity of this lipase.

Candida↗

PubMed1993

Comparison of ondansetron versus placebo to prevent postoperative nausea and vomiting in women undergoing ambulatory gynecologic surgery.

BACKGROUND: Postoperative nausea and emesis, especially in ambulatory surgical patients, remains a troublesome problem. This study was performed to compare the incidence of nausea and emesis during the 24-h postoperative period in ondansetron-treated patients versus placebo-treated patients. METHODS: Using a randomized prospective double-blind study design, women between the ages of 18 and 70 yr undergoing gynecologic surgical procedures with general opioid anesthesia on an outpatient basis were enrolled. Ondansetron or placebo was administered prior to induction of anesthesia. Patients were stratified according to history of nausea and emesis during previous exposure to general anesthesia and randomized to dose received. RESULTS: Data from the 544 women showed that all doses of intravenous ondansetron tested (1, 4, and 8 mg) were significantly more effective (62%, 76%, and 77%, respectively) than placebo (46%) in reducing the incidence of emesis following surgery until 24 h after recovery room entry. All these doses were more effective than placebo in patients with no prior history of emesis following surgery and the 4- and 8-mg doses were more effective than placebo in patients with a prior history of emesis following surgery. All doses of ondansetron tested were generally well tolerated with adverse events, clinical laboratory tests, and recovery room vital signs similar to those of placebo. Serum aspartate transaminase (AST) was increased in five patients (1 mg, 2 patients; 4 mg, 1 patient; 8 mg, 2 patients). In the three patients in whom subsequent analysis were performed, the serum AST had decreased to preoperative levels. CONCLUSIONS: Ondansetron given intravenously to prevent postoperative nausea and emesis was highly effective in the 4- and 8-mg doses in women having ambulatory gynecologic surgery.

Adult↗

PubMed1992

Prophylactic intravenous ondansetron in female outpatients undergoing gynaecological surgery: a multicentre dose-comparison study.

The efficacy and safety of prophylactic intravenous ondansetron in preventing postoperative nausea and vomiting was investigated in a randomized, stratified, double-blind, placebo-controlled, dose-comparison study of 580 ASA physical class I and II female outpatients undergoing gynaecological surgery and receiving general anaesthesia. Patients received either ondansetron 1, 4 or 8 mg, or placebo i.v. immediately prior to a standardized technique for induction and maintenance of anaesthesia. All patients were intubated and received nitrous oxide and a narcotic. All doses of ondansetron were significantly more effective than placebo in preventing emesis over the 24 h postoperative period. Ondansetron significantly decreased nausea and emesis scores over 24 h postoperatively without causing sedation. No changes in laboratory parameters (haematology, blood chemistry, and liver enzymes) or vital signs (heart rate, blood pressure, and respiratory rate) were observed. Headache and dizziness were the most common side-effects; however, their incidence was the same as with placebo. Ondansetron was generally well tolerated, as evidenced by an adverse event, laboratory safety, and vital sign profile similar to placebo. Ondansetron 4 mg was found to be the optimal prophylactic i.v. dose for female outpatients over the entire 24 h postoperative period. Higher doses may offer an added benefit in some patients, such as those with a history of nausea and vomiting following general anaesthesia.

Adult↗

PubMed1989

[Morphology of tubulointerstitial nephritis].

The morphological picture of interstitial (tubulointerstitial) nephritis is not rare when renal biopsies or necropsies are evaluated. According to experience assembled during examinations of renal biopsies (a group of 1484 biopsies) in particular biopsies with morphological changes of the character of interstitial nephritis (144 in the group) and according to findings reported in the available literature, the authors submit an account of changes encountered in a large group of interstitial nephrites. The need of such an account ensues in particular from clinical practice where the morphological picture can be decisive for establishing the correct diagnosis in cases where other, in particular clinical and biochemical examination procedures, do not suffice.

Acute Disease↗

PubMed1988

Interaction of N-acetyl-4-epi-D-neuraminic acid with key enzymes of sialic acid metabolism.

In spite of the axially orientated hydroxy group at C-4, the benzyl alpha-glycoside of N-acetyl-4-epi-D-neuraminic acid (4-epi-NeuAc) is a substrate for sialidases from Vibrio cholerae, Clostridium perfringens, and Arthrobacter ureafaciens, although to an extent which differs depending on the enzyme. Surprisingly, V. cholerae sialidase is by far the slowest acting enzyme; this is in contrast to its usual behavior. Fowl plague virus sialidase and bovine testis sialidase also cleave this glycoside slowly. 4-Epi-NeuAc is not a substrate for N-acetylneuraminic acid aldolase from C. perfringens but reversibly inhibits the enzyme with a Ki = 2.3 mM. The N-acetylneuraminic acid analogue is not converted to the corresponding CMP-glycoside by CMP-sialic acid synthase from bovine brain; however, it is an effective reversible inhibitor of the enzyme. The kinetic properties were analyzed with an assay system at pH 9 as well as an assay system at pH 7.5. The results from Dixon and Hanes plots did not agree. Therefore, no conclusions about the mechanism of the inhibition could be reached. This is the first reported sialic acid analogue which can act as an inhibitor of CMP-sialic acid synthase.

Animals↗

PubMed1985

Cavernosography in diagnosis of penile metastases secondary to bladder cancer.

This is a case report of transitional cell carcinoma of the bladder which metastasized to lymph nodes, bone, and the penis. The penile metastases were demonstrated by cavernosography. Secondary tumors in the penis are rare. They presage a bad prognosis and a rapid demise; the patients survive an average of four months.

Aged↗

PubMed1985

Endoscopic drainage of pancreatic pseudocysts.

Enlarging pancreatic pseudocysts, as well as those that develop complications such as bleeding, leak, infection, and intestinal or biliary obstruction, require treatment. This treatment is usually surgical and consists of internal or external drainage or, less commonly, excision. Transcutaneous aspiration with or without drain placement has also been reported. We describe four cases of endoscopic cystogastrostomy and cystoduodenostomy undertaken in high risk patients who had either failed previous surgery (two) or were initially refused surgery because of prohibitive operative risk (two). Technique, limitations, and potential use of this procedure are discussed.

Adult↗

PubMed1984

Venography during endoscopic injection sclerotherapy of esophageal varices.

Utilizing an equal mixture of 5% sodium morrhuate and 60% renografin, we studied four patients during a total of nine sessions of injection sclerotherapy of esophageal varices to determine radiographically the fate of injected sclerosant. Despite attempted intravariceal injections, 44% resulted in local and presumably paravariceal accumulation of contrast material within the esophageal wall. During 42% of injections, contrast material was rapidly cleared in a cephalad direction and proximal balloon compression of the esophagus did not prevent cephalad flow of sclerosant. In 14% the injected material was rapidly cleared in a caudal direction toward the gastric veins. This technique may be useful in future evaluations of the efficacy of various methods of injection sclerotherapy of esophageal varices.

Contrast Media↗